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PUBLICATIONS - CROI 2020
ACTG TO PRESENT NEW HIV AND TB RESEARCH AT CROI 2020

This month, ACTG is highlighting studies to be featured at the Conference on Opportunistic Infections (CROI) 2020. ACTG will make 28 presentations at the premier global health research conference, taking place in Boston from March 8-11, including data on the impact of chronic antiretroviral therapy (ART) on a novel metric of the HIV reservoir, predictors of multidrug resistant (MDR)-TB in resource-limited settings, findings from the first HIV cure trial that exclusively enrolled women, and the impact of contraceptives on vaginal microbiome and TB drugs.
 
“The ACTG has led research on HIV and its co-infections and comorbidities since the beginning of the epidemic, more than 30 years ago,” said ACTG Chair Judith Currier, M.D., MSc of the University of California Los Angeles. “The studies being presented at CROI this year reflect the diversity of ACTG’s research portfolio and demonstrate our commitment to addressing the full range of issues affecting people living with HIV. These studies provide insights into HIV cure, TB, the interaction between contraception and HIV treatment, sex differences, and co-morbidities in people living with HIV.”
 
The ACTG abstracts that will be presented at CROI 2020 demonstrate ACTG’s continued impact on the understanding of HIV pathogenesis, clinical interventions, clinical care, and the health of people living with HIV. These presentations are arranged by topic below.
 
ORAL PRESENTATIONS AND THEMED DISCUSSIONS
INTACT PROVIRAL DNA LEVELS DECLINE IN PEOPLE WITH HIV ON ANTIRETROVIRAL THERAPY (ART) (ACTG 5321; Oral Abstract Session 0-06: Targeting the Persistent HIV Reservoir, Tuesday, March 10 10:00 am – 12:00 pm) Rajesh T. Gandhi, et al. (rgandhi@mgh.harvard.edu) Topic: HIV Cure, the Reservoir, and Persistence
The intact proviral DNA assay is a novel metric of the HIV reservoir. This study shows that intact proviral DNA levels decline for people on chronic ART and examines the relationship of that decline to other metrics of HIV persistence and immune activation.

PREDICTORS OF TUBERCULOSIS INFECTION IN MDR-TB HOUSEHOLD CONTACTS 15 YEARS OLD (ACTG 5300/IMPAACT2003; Oral Abstract Session 0-12: Tuberculosis, Opportunistic Infections, and HIV Testing, Wednesday, March 11 10:00 am – 12:00 pm) Soyeon Kim, et al. (skim@sdac.harvard.edu) Topic: Tuberculosis
This presentation provides insights into predictors of active TB infection among household contacts of individuals with MDR-TB.
 
EFFECT OF TAMOXIFEN ON VORINOSTAT-INDUCED HIV RNA EXPRESSION IN WOMEN ON ART (ACTG 5366; Themed Discussion Session TD-06: Curative Strategies: Trials and Tribulations, Tuesday, March 10 1:30 pm – 2:30 pm) Eileen Scully, et al. (escully1@jhmi.edu) Topic: HIV Cure, the Reservoir, and Persistence
A5366 is the first study to examine a strategy to reduce the HIV reservoir exclusively in women using a hormone-modulating approach. Since estrogen in women blocks the expression of HIV when researchers try to ‘turn on’ the latent reservoir in women living with HIV, A5366 examines whether tamoxifen and vorinostat can reverse latency.
 
A COMBINED ESTROGEN/PROGESTIN VAGINAL RING IMPROVES VAGINAL MICROBIAL COMMUNITIES (ACTG 5316; Themed Discussion Session TD-15: Making Sense of it All: HIV Susceptibility in the Female Genital Tract, Wednesday, March 11, 1:30 pm – 2:30 pm) Nicole H. Tobin, et al. (ntobin@mednet.ucla.edu) Topic: Contraception
This presentation explores the relationship between the use of hormone-base intravaginal rings and vaginal flora.
 
ANTIRETROVIRAL AND RIFAMPICIN CO-TREATMENT AFFECTS DMPA EXPOSURE: DOSING IMPLICATIONS (ACTG 5338; Themed Discussion Session TD-13: The Long and Short of it: What’s Next for Long-Acting Drugs, Wednesday, March 11, 1:30 pm – 2:30 pm) Jose Francis, et al. (jose.francis@uct.ac.za) Topic: Contraception
Because TB coinfection among pregnant women living with HIV is associated with poor outcomes, effective contraception to prevent unintended pregnancy is important. This study examines the impact of HIV and rifampicin-based TB therapy on depot medroxyprogesterone acetate (DMPA) levels when used as an injectable contraceptive.
 
POSTER PRESENTATIONS
HIV Cure, the Reservoir, and Persistence
RISK AND PREVALENCE OF RESIDUAL VIREMIA AFTER cART IN RESOURCE-LIMITED COUNTRIES (NWCS 425; Poster Session P-E02: Measuring the HIV Reservoir, Monday, March 9, 2:30 pm – 4:00 pm) Sivaporn Gatechompol, et al. (sivaporn.k@hivnat.org)
This study compares factors associated with residual single copy viremia in people living with HIV who are virally suppressed on ART between the United States and resource-limited settings.
 
TELMISARTAN DECREASES MONOCYTE CX3CR1 EXPRESSION IN TREATED HIV INFECTION (ACTG 5317; Poster Session P-M02: Adipose Tissue and Obesity, Tuesday, March 10, 2:30 pm – 4:00 pm) Jordan E. Lake, et al. (jordan.e.lake@uth.tmc.edu)
Telmisartan is an angiotensin receptor blocker with anti-inflammatory properties, especially in adipose tissue. This presentation evaluates whether telmisartan improves inflammatory and obesity markers in patients on ART.
 
AMINOBISPHOSPHONATES REVERSE LATENCY IN HIV-SEROPOSITIVE INDIVIDUALS (NWCS 464; Poster Session P-E07: HIV Curative Strategies: In Vitro Studies, Tuesday, March 10, 2:30 pm – 4:00 pm) Natalia Soriano-Sarabia, et al. (nataliasorsar@email.gwu.edu)
Aminobisphosphonates, which are used to treat osteoporosis, may reverse latency in chronic HIV infection due to disruptions in cell signaling. This study examines that association for the first time.  
 
TH2 CYTOKINES ARE ASSOCIATED WITH HIGHER LEVELS OF INTACT PROVIRUSES ON ART (ACTG 5321; Poster Session P-E10: Immune Pressure on the HIV Reservoir, Wednesday, March 11, 2:30 pm – 4:00 pm) Joshua C. Cyktor, et al. (jcc114@pitt.edu)
This study examines the relationship between levels of various cytokines among people on ART and different metrics of the HIV-1 reservoir. 
 
MODELING HIV RESERVOIR DECLINE AFTER ART INITIATION AS A FUNCTION OF NK CELL FEATURES (NWCS 441; Poster Session P-E10: Immune Pressure on the HIV Reservoir, Wednesday, March 11, 2:30 pm – 4:00 pm) Elena Vendrame, et al. (elenaven@stanford.edu)
HIV DNA levels decline after ART initiation, and this study examines factors associated with that decline, including natural killer cells.
 
Viral Control with or without Structured Treatment Interruptions
FACTORS ASSOCIATED WITH VIRAL CONTROL AFTER STRUCTURED TREATMENT INTERRUPTION (NWCS 470; Poster Session P-E04: Insights from Analytical Treatment Interruptions, Monday, March 9, 2:30 pm – 4:00 pm) Nikolaus Jilg, et al. (njilg@partners.org)
Structured treatment interruptions (STIs) will be a critical strategy to determine if HIV remission or cure efforts are successful. This study examines the factors immediately following STIs that predict longer periods of virologic control.
 
HIV POST-TREATMENT CONTROL DESPITE PLASMA VIRAL EVOLUTION AND DUAL INFECTION (NWCS 470; Poster Session P-E04: Insights from Analytical Treatment Interruptions, Monday, March 9, 2:30 pm – 4:00 pm) Behzad Etemad, et al. (betemad@bwh.harvard.edu)
HIV post-treatment controllers (PTCs) serve as models for sustained HIV remission and may provide clues for HIV remission or cure studies. This study examines plasma virus composition and diversification within HIV PTCs.
 
FREQUENCY OF POST-TREATMENT CONTROL VARIES BY ART RESTART AND VIRAL LOAD CRITERIA (NWCS 380; Poster Session P-E04: Insights from Analytical Treatment Interruptions, Monday, March 9, 2:30 pm – 4:00 pm) Jesse M. Fajnzylber et al. (jesse_fajnzylber@dfci.harvard.edu)
Analytic treatment interruptions (ATI) are critical strategies to examine the efficacy of HIV remission or cure strategies. This study examines an interactive tool for estimating viral rebound timing in the setting of an ATI.
 
Tuberculosis
GEOGRAPHIC AND INDIVIDUAL RISK FACTORS FOR TB OR DEATH IN THE BRIEF-TB TRIAL (ACTG 5279; Poster Session P-N02: Latent TB Infection: Risk Factors, Treatment, and Prevention, Monday, March 9, 2:30 pm – 4:00 pm) Cynthia Riviere, et al. (criviere@ghesiko.org)
The original A5279 trial compared one month of isoniazid and rifapentine to nine months of isoniazid for TB prevention in resource-limited settings. This follow-up presentation explores clinical, demographic, and geographic factors associated with TB acquisition, TB-related death, and death in each group.
 
Comorbidities
ADVANCED GLYCATION END PRODUCTS ASSOCIATED WITH CARDIOMETABOLIC RISK ON ART (ACTG 5260; Poster Session P-L01: Inflammatory Biomarkers and Cardiovascular Outcomes, Monday, March 9, 2:30 pm – 4:00 pm) Vanessa El Kamari, et al. (Vanessa.ElKamari@UHhospitals.org)
This study evaluates changes in serum advanced glycation end products (AGEs), usually associated with aging, in the ACTG 5257 trial after ART initiation with one of three NNRTI-based regimens.
 
TRICARBOXYLIC ACID METABOLITES PREDICT METABOLIC COMORBIDITIES AND DEATH IN AGING PWH (NWCS 447; Poster Session P-M03: Metabolic Complications, Monday, March 9, 2:30 pm – 4:00 pm) Corrilynn O. Hileman, et al. (chileman@metrohealth.org)
Monocyte activation may contribute to inflammatory and metabolic changes among people aging with HIV. This study analyzes associations between concentrations of monocyte activation markers and comorbidities in the HIV Infection, Aging, and Immune Function Long-Term Observational (HAILO) study.
 
PREDICTIVE VALUE OF THE CD8 COUNTS AND CD4/CD8 RATIO AT TWO YEARS OF SUCCESSFUL ART (DACS 322.1; Poster Session P-Q05: T Cell Patterns, Monday, March 9, 2:30 pm – 4:00 pm) Sergio Serrano-Villar, et al. (sergio.serrano@salud.madrid.org)
Although CD4 cell counts predict clinical events, there is variability in the predictive power of CD8+ T cell counts and CD4/CD8 ratios on clinical outcomes in HIV. This study examines these factors in relation to clinical events on suppressive ART.
 
GUT INTEGRITY MARKERS AND ASSOCIATIONS WITH ADIPOSITY IN PEOPLE WITH AND WITHOUT HIV (ACTG 5260s; Poster Session P-M02: Adipose Tissue and Obesity, Tuesday, March 10, 2:30 pm – 4:00 pm) Allison Ross Eckard, et al. (eckarda@musc.edu)
Fat accumulation after ART initiation remains a serious problem among people living with HIV, but little is known about the pathophysiology of this process, especially with Integrase Strand Transfer Inhibitors. This presentation assesses the relationship between gut integrity markers and body composition for the first time. 

A CROSS-SECTIONAL ANALYSIS OF ANTIRETROVIRAL REGIMEN ACTIVITY IN CEREBROSPINAL FLUID (ACTG 5321; Poster Session P-G03: Pharmacokinetics and Pharmacodynamics in Special Populations and Body Sites, Tuesday, March 10, 2:30 pm – 4:00 pm) Courtney V. Fletcher, et al. (cfletcher@unmc.edu)
This study analyzes the distribution of different antiretrovirals (ARVs) in cerebrospinal fluid and the relationship between that distribution and biomarkers of HIV persistence and inflammation in the cerebrospinal fluid.

T-CELL AND MONOCYTE ACTIVATION CORRELATE AND DECLINE DURING HCV THERAPY FOR HCV-HIV (ACTG 5329; Poster Session P-J06: HCV After the SVR: Gone but Not Forgotten, Tuesday, March 10, 2:30 pm – 4:00 pm) Ann Auma, et al. (awa28@case.edu)
Successful hepatitis C (HCV) therapy has been associated with partial or complete normalization of immune activation during mono-HCV infection. This presentation shows that successful therapy for HCV among patients with HIV-HCV co-infection similarly leads to a decline in markers of immune activation, despite the ongoing HIV.

PLASMA CITRATE AND SUCCINATE PREDICT NEUROCOGNITIVE IMPAIRMENT IN OLDER PWH (NWCS 447; Poster Session P-F02: Neurocognition: Biomarkers, Therapies, and Outcomes, Tuesday, March 10, 2:30 pm – 4:00 pm) Corrilynn O. Hileman, et al. (chileman@metrohealth.org)
This study evaluates the effect of specific neuroinflammatory markers on neurocognitive impairment among older people living with HIV.

PREVALENCE OF PHYSICAL FUNCTION IMPAIRMENT AND FRAILTY IN MIDDLE-AGED PWH (ACTG 5361; Poster Session P-M08: Functional Status and Frailty, Wednesday, March 11, 2:30 pm – 4:00 pm) Triin Umbleja, et al. (tumbleja@sdac.harvard.edu)
People living with HIV have an increased risk of falls, hospitalizations, and mortality due to frailty. This study evaluates the risk factors for physical function impairment among patients with HIV at low to moderate cardiovascular risk.
 
PRINCIPAL COMPONENTS ANALYSIS TO IDENTIFY BIOMARKERS PREDICTIVE OF NON-AIDS EVENTS (NWCS 411; Poster Session P-B08: Non-AIDS Consequences of HIV Infection, Wednesday, March 11, 2:30 pm – 4:00 pm) Carlee Moser, et al. (cmoser@sdac.harvard.edu)
In this presentation, biomarkers of monocyte and macrophage activation are examined in relationship to non-AIDS events among individuals living with HIV.
 
TOTAL HIV DNA LEVELS DO NOT PREDICT NON-AIDS-DEFINING EVENTS (NWCS 411; Poster Session P-B08: Non-AIDS Consequences of HIV Infection, Wednesday, March 11, 2:30 pm – 4:00 pm) Colline Wong, et al. (cwong22@bwh.harvard.edu)
While total HIV DNA levels predict the size of the HIV reservoir, this study shows that this biomarker is not associated with non-AIDS defining events among people living with HIV.
 
Sex Differences
SEX-SPECIFIC ANALYSES IN ORAL ABSTRACTS FROM CROI 2019 (A5001; Poster Session P-Q02: HIV in Key Populations, Monday, March 9, 2:30 pm – 4:00 pm) William R. Short, et al. (wshort@pennmedicine.upenn.edu)
Globally, women account for more than half of all people living with HIV yet remain underrepresented in research. CROI guidelines (starting in 2018) specifically recommend reporting sex distribution and sex-adjusted analyses, but adherence to these guidelines has been relatively poor. This updated analysis examines adherence to these guidelines among oral abstracts from CROI 2019.
 
DYNAMICS OF HIV-SPECIFIC T-CELLS ON DURABLE ART DIFFER BY ANTIGEN RECOGNIZED & BY SEX (ACTG 5321; Poster Session P-D08: Impact of Antiretrovirals on the Immune Response, Wednesday, March 11, 2:30 pm – 4:00 pm) Eva M. Stevenson, et al. (ems2200@med.cornell.edu)
In order to advance understanding toward HIV cure, sex differences must be examined to determine whether cure strategies will differ by sex. This study examines differences in HIV-specific T cell responses by sex among chronically treated patients on ART.
 
HIV Diagnosis/Predictors of Clinical Outcomes
INFLAMMATION AND MITOCHONDRIAL DYSFUNCTION NOT NRTIS DRIVE EVENTS IN ACTG A5241 (NWCS 423; Poster Session P-M10: Epigenetic and Mitochondrial Toxicities, Tuesday, March 10, 2:30 pm – 4:00 pm) Carl J. Fichtenbaum, et al. (fichtecj@ucmail.uc.edu
A recent ACTG study found that among people living with HIV experiencing treatment failure, the treatment arm that added an NRTI to a regimen of two or more ARVs had more deaths and clinical events than the arm that did not. However, inflammation and mitochondrial dysfunction seem to drive these events (not the NRTIs) in this study.

NOVEL CRITERIA FOR DIAGNOSING ACUTE HIV IN A MULTI-NATIONAL ART INITIATION STUDY (ACTG 5354; Poster Session P-R06: Diagnosing Early HIV Infection, Wednesday, March 11, 2:30 pm – 4:00 pm) Trevor A. Crowell, et al. (tcrowell@hivresearch.org)
ART initiation during acute HIV infection (AHI) limits the size of the HIV reservoir, but identifying patients with AHI can be logistically challenging. This presentation evaluates a novel way to diagnose AHI incorporating modern diagnostic algorithms to facilitate early treatment.  
SPOTLIGHTS
INVESTIGATOR SPOTLIGHT
Dr. Rachel Bender Ignacio

ACTG Investigator Dr. Rachel Bender Ignacio is an Assistant Professor in the Division of Allergy and Infectious Diseases at the University of Washington (UW) and Associate in the Vaccine and Infectious Diseases Division of the Fred Hutchinson Cancer Research Center (FHCRC). She recently became the Associate Director of the UW ACTU CRS, where she is really excited to have the opportunity to help plan a forward vision for the Seattle-Lausanne CTU. She joined the ACTG in 2019 and was recently elected to the ITSG as a Member in Training for the first year. She was also recently elected to the Board of Directors for HIVMA.
 
Dr. Bender Ignacio completed Internal Medicine training at Massachusetts General Hospital and Infectious Diseases fellowship and an MPH in Epidemiology at UW. She started working in HIV-associated malignancies with the Global Oncology program at the Fred Hutchinson Care Center in 2013, with a focus on HIV diagnosis and ART strategy during cancer treatment. She currently holds an NIAID-funded K23 research grant to study the role of inflammation and viral-coinfections in HIV acquisition and establishment of the HIV latent reservoir. She was awarded a CFAR New Investigator Award in 2018 for parallel work addressing similar questions for TB infection and immune activation with respect to HIV acquisition. She is working with other investigators at UW/FHCRC and the Peru CTU to evaluate clinical, immunologic, virologic, and microbiome outcomes in the MERLIN study (independent of the ACTG), which follows persons who were randomized to start ART during primary HIV or six months later.

Dr. Bender Ignacio is excited to work on inflammatory and metabolic consequences of HIV and ART through the ACTG. She continues to work on a variety of topics in HIV-associated malignancy, including through a proposed Data Analysis Concept Sheet (DACS) on KSHV Inflammatory Cytokine Syndrome within two KS-related ACTG studies. Her other NIH-funded studies include the National Cancer Institute's U.S.-Latin American-Caribbean Clinical Trials Network for Prevention of HPV-related Cancers in people living with HIV and the AIDS Malignancy Consortium.

 

CAB MEMBER SPOTLIGHT
Cebisile Nkosi, South Africa


Cebisile Nkosi joined the ACTG in 2012 from Durban, South Africa. She became involved because of family members who died from AIDS-related complications. She lost four family members during her first year at university. She was studying marketing at the time and didn’t know much about HIV. “My family members told me their stories and inspired me change my course of study to learn more about HIV, so I could help them. Now I am inspired to help others,” she said.

Cebisile focuses her energy on youth. She describes much of her advocacy work as being aimed at helping youth who are impacted by unplanned pregnancies and perinatal HIV transmission. She says that access to ART is the most pressing treatment issue in her community.

Cebisile wants to be remembered as someone who supported her family and community. “I want to be remembered for making my community better than it was before, because of my involvement with the ACTG,” she said. “My hope is to get all of our communities the best treatment. My hope is to cure every illness and challenge we are facing. I hope the ACTG continues to help our communities be better than before—healthier, more knowledgeable, and more involved.” 
ACTG SITE SPOTLIGHT
PHRU-MATLOSANA, South Africa

The PHRU-Matlosana Clinical Research Site (CRS) is an ACTG site located in the MDR-TB Unit on the campus of the Tshepong Hospital in Matlosana, South Africa. The site successfully kick-started recruitment for PHOENIx/A5300B in December 2019 and continues to screen and enroll MDR-TB index cases with household contacts. 
 
The Matlosana CRS conducted its first clinical study in 2007 with just two employees; they recruited participants to an observational study assessing mortality among in-patients with TB. A sub-study of this observational cohort was the first to report test characteristics of urinary lipoarabinomannan (LAM) assay among in-patients with TB. Since then, the site has grown substantially and is now capable of conducting varying types of studies. 
 
The Matlosana CRS team writes about their experience joining ACTG: “Our team has joined ACTG with enthusiasm about continuing the work that ACTG have been doing over so many years. Since joining the ACTG, we have had more resources available to our site, which means that we are better able to conduct high-quality clinical trials, and better reach the community we live in. This increased knowledge will result in our being able to add on other sub-studies to our current protocols and help improve lives through research.
 
“Our experienced staff is well trained to recruit and retain a large number of participants for clinical trials. Our Matlosana CAB, headed by Mr. Abram Maubane, ensures that we have close links to community representatives. Our team includes Dr. Neil Martinson (CRS Leader), Dr. Tumelo Moloantoa (CRS coordinator), Mr. Itumeleng Holele (study coordinator), Dr. Oteng Letlape (Sub-Investigator), the CTU professional nurse, recruiter, and a general research assistant. We have three pharmacists working in the research pharmacy, which also assists the hospital’s MDR pharmacy. Our CRS members strategically work together to identify, pre-screen, and enroll participants according to our recruitment plan.”


 
 
NEWS TO SHARE?

Do you have interesting ACTG-related news to share? Has your site done something exceptional? What’s the latest news about your study? Do you have job postings or any other ACTG-related information? We want to know! Please submit your news to ACTG Leadership & Operations Center Communications Specialist Karen Hoffman.
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